TY - JOUR
T1 - Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation
AU - Gregorini, Marilena
AU - Bosio, Francesca
AU - Rocca, Chiara
AU - Corradetti, Valeria
AU - Valsania, Teresa
AU - Pattonieri, Eleonora Francesca
AU - Esposito, Pasquale
AU - Bedino, Giulia
AU - Collesi, Chiara
AU - Libetta, Carmelo
AU - Frassoni, Francesco
AU - Dal Canton, Antonio
AU - Rampino, Teresa
PY - 2014/10/3
Y1 - 2014/10/3
N2 - Background: In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. Methods: MSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated. Results: In grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression. Conclusions: Our results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.
AB - Background: In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. Methods: MSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated. Results: In grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression. Conclusions: Our results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.
KW - Acute kidney rejection
KW - Experimental model
KW - Hepatocyte growth factor
KW - Macrophage stimulating protein
KW - Mesenchymal stromal cells
KW - Scatter factors
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U2 - 10.1186/s12865-014-0044-1
DO - 10.1186/s12865-014-0044-1
M3 - Article
C2 - 25277788
AN - SCOPUS:84907952454
SN - 1471-2172
VL - 15
JO - BMC Immunology
JF - BMC Immunology
IS - 1
M1 - 44
ER -